Lifeboat Foundation LifePreserver

The LifePreserver program is designed to bring you the latest
information about aging research and the progress towards treating
age-related diseases. This program also aims to bring you practical
information about the steps you can take now to slow the aging process
and delay the onset of age-related disease. Hopefully by taking these
measures you can increase your chances of being in good health when more
robust life-extending and life-enhancing technologies become available
over the next couple of decades.

So What is Aging?

People talk about aging a lot, but what do they really mean and what
exactly is aging?

According to modern science, aging is the accumulation of damage/error
that the body cannot completely eliminate, due to the imperfections of
its protection and repair systems. As a result, bodily functions start to
deteriorate, leading ultimately to the development of age-related
diseases, such as cancer, stroke, type 2 diabetes, heart diseases,
Alzheimer’s disease, osteoarthritis, osteoporosis, and others.

Aging is made of a number of distinct and connected processes that
collectively produce the phenomenon we know as aging. Many people think
that aging is too complex and too large a problem to do anything about
it, however, as with any large problem the best approach is to divide
the problem up into actionable pieces. When problems, no matter how
large, are broken down in this way it becomes easier to understand how
we might deal with them.
Once you begin to understand the processes of
aging it becomes possible to understand the ways we might intervene
against them in order to treat and prevent age-related diseases, hence
enabling people to live healthier lives for longer.

To help you visualize what aging is, the aging processes are divided into
distinct categories known as hallmarks, what follows is a simple summary
of these
hallmarks of aging.

The Hallmarks of Aging

Genomic instability: Exposure to environmental hazards such as
radiation, chemicals, or other toxic agents over time can damage our
genome, as can things like DNA replication errors or oxidative stress.
Evolution has given us a robust system of DNA repair mechanisms,
however, DNA damage accumulates over the course of our lives, causing
mutations in cells that can potentially lead to cancer.

Telomere attrition: Like the plastic tips on your shoelaces,
telomeres protect the terminal ends of our chromosomes from damage. The
normal DNA replication mechanisms in the majority of our cells are not
able to copy the ends of our DNA completely, so the repetitive DNA
sequences of the telomere region shorten with each cell division. After
a number of replications the telomeres become critically short and cell
stop dividing — this reduces the ability of tissues to regenerate as we
age.

Epigenetic alterations: Have you ever wondered how our various
tissues and organs can appear so different from one another, since our
DNA is exactly the same in all cells in our body? This is because our
DNA is modified with epigenetic information that activates or silences
the expression of particular genes as needed by the different tissue
types. For example, if a cell needs to become a lung cell, epigenetics
ensures that the parts of the genome specific to lung cells are
expressed, while the parts specific to other cell types are silenced.
The aging process alters our epigenetic code, which leads to changes in
gene expression that then cause normal cells to become dysfunctional.
For example, in the immune system, this could change the balance between
activating and suppressing the immune cells, causing our bodies to
become more vulnerable to invading pathogens.

Loss of proteostasis: In our cells, proteins are constantly being
created and destroyed in a process known as proteostasis. Proteins are
like tiny tools which have to be assembled correctly to perform their
various cellular functions. An important part of that assembly is
folding these proteins into the proper shapes. Various mechanisms help
to stabilize and ensure proteins are correctly folded, as well as
removing and destroying improperly shaped proteins which would otherwise
accumulate and damage cells. Aging causes these mechanisms to become
less efficient over time, This leads to the accumulation of misfolded
proteins causing dysfunction or even cell toxicity as seen in diseases
such as Alzheimer’s.

Deregulated nutrient sensing: When nutrients are abundant, cells
and tissues respond by storing energy and growing; when nutrients are
scarce the body activates hormesis, a stress induced repair mechanism
that aids survival. In the case of diabetes and obesity, cells are
constantly exposed to abundant levels of nutrients, resulting in the
cellular mechanisms that sense nutrients to become desensitized.
Deregulation of the nutrient sensing pathway also occurs during the
aging process, and as a result, cells do not respond properly to the
signals that normally regulate energy production, cell growth, and other
crucial cellular functions.

Mitochondria power your body

Mitochondrial dysfunction: Free radicals, also known as reactive
oxygen species (ROS), are a natural byproduct of energy production by
the mitochondria in our cells. Although they have a role in cellular
signaling, in high doses free radicals can be harmful to the cell. The
free radical theory of aging suggests that over time, increasing levels
of ROS production damages mitochondria causing dysfunction, even more
ROS production, and cellular deterioration. Mitochondrial dysfunction
also appears to affect other cellular signaling pathways and functions.
Ultimately the cell becomes increasingly poor at producing energy, and
simultaneously, ROS levels rise, damaging the other parts of the cell.
Thus, mitochondrial dysfunction is implicated in a number of age-related
conditions such as myopathies and neuropathies.

Cellular senescence: When cells receive enough damage, whether from DNA
damage or telomere shortening, they enter a state of stable growth
arrest known as cellular senescence. This is a safety measure to stop
damaged cells from becoming cancerous, but it also prevents old, worn
out cells from remaining in circulation. Normally the immune system
removes these unwanted cells but as we age the immune system stops
removing them and their numbers grow. Senescent cells secrete
pro-inflammatory signals that damage the cell and can even cause nearby
healthy cells to become senescent too. This leads to chronic tissue
inflammation that contributes to conditions like osteoarthritis and
kidney dysfunction. This means the safety measure protecting us in youth
from cancer actually fuels the aging process as we grow older.

The microbivore, an artificial white cell, floats along in the
bloodstream until it encounters a pathogen. This is one of the radical
life-extending and life-enhancing technologies that could cure
cellular senescence in the next couple decades.
Courtesy, Zyvex Corp and
Robert A. Freitas Jr.

Stem cell exhaustion: One of the most obvious consequences of
growing old is increasingly poor recovery from injury. This is caused by
a decline in the ability of our stem cells to replace damaged tissues.
Your stem cells spend most of their time in a dormant state in their
niche, but when they are awakened to heal wounds and restore tissues,
they also become susceptible to telomere shortening, DNA damage, and
cellular senescence. Over time this results in stem cell exhaustion as
the pool of stem cells runs out.

Altered intercellular communication: To grow and function
normally, our cells need to constantly communicate with each other,
secreting signaling molecules to their neighbors or even sending
molecular messengers through the bloodstream to distant cells and
tissues. Aging alters not only the signals that are sent by cells, but
also the ability of cells to receive such signals. This dysfunctional
communication leads to chronic tissue inflammation, failure of the
immune system to recognize and clear pathogens or dysfunctional cells,
and also reduces the ability of stem cells to repair tissue due to
being inhibited.

Can we address these hallmarks to prevent age-related disease?

The weight of scientific evidence is increasingly suggesting that yes, we
can likely intervene directly on these processes in order to combat
age-related diseases. While our knowledge of the aging process is not
complete, it has reached the stage where meaningful progress is being
made towards interventions. In some cases, such as senescent cell removal
(senolytics) and stem cell therapies, that progress is already well
advanced and entering clinical trials. There are solutions to each of
these hallmarks of aging and it is really only a matter of time before
practical therapies are developed to address each one. This would result
in better ways to treat age-related diseases and potentially leading to
healthier, independent, and longer lives for everyone.

OK, so what are we waiting for?

There are a number of bottlenecks for us to solve if we are to succeed
and deliver powerful therapies that directly address the aging processes
in humans.

1

Lack of scientific knowledge on the aging processes and
potential ways to address them. Knowledge like this is usually born in
the field of basic science. The studies of this type are high-risk ones
(they are intended to find out what works and what doesn’t), the
positive result is not guaranteed, and even if the scientific group is
lucky enough to get a positive result, these studies are usually done in
cells or in animals — and never in humans. There is no final product one
can start selling after the study, which is why business is not very
keen to fund this type of research: technically, this is a donation, not
an investment. Here is the dilemma: the knowledge created in these
studies is crucial for us to progress to the drug development stage, but
there are not many people who aspire to become philanthropists and save
the day for the whole of humanity.

2

Normally it is the government who finances basic science, but
breakthrough projects have less chance to get support. It is true the
state is funding research institutions and awarding research grants. But
research on aging is relatively new and therefore there are not many experts among
the decision-makers in the grant system who can assess the breakthrough
projects aimed at the hallmarks of aging and truly understand their
potential. This is why these kinds of projects have less support from
the government than the mainstream studies of a single disease like
Alzheimer’s or cancer. Without appreciation from the government and
support from business, the field of aging research can only rely on one
funding source: the general public.

3

The number of ardent supporters of aging and longevity studies
is relatively small due to slow information dissemination from the
scientists to the public. Most people still believe there is nothing we
can do about biological aging, and so they see these studies as
researchers simply feeding their scientific curiosity. Education
regarding the plausibility and desirability to defeat aging takes time
and a lot of effort. It cannot be done by the scientists themselves (as
their job is to work in the lab, not to make shows), and here is where
advocacy groups and science popularizers should step in. However, people
tend to forget that the best results can only be achieved if a group is
well-organized, disciplined, and uses evidence-based practices in all
activities, from planning and management to crowdfunding, educating, and
lobbying. Steady progress requires a mindful and responsible approach
from each person joining an advocacy group — which is sadly rarely seen.

4

If it is not the lack of hard-working activists that is
holding progress back, then it is the wrong messaging. Many members
of our community prefer to profess their desire for indefinite lifespans
directly, shocking the public and making the whole movement appear to
consist of radicals, daydreamers, and windbags. There are a number of
sociological studies that show just how important it is to properly
explain the connection between aging and age-related diseases, and the
causal relationship between aging prevention, health improvement, and
longevity — longevity being a side-effect of better health. Being
patient and addressing concerns people may have in relation to longer
lives is another important job which is rarely done properly. Despite
the fact that most of these sociological studies are available to read
and have even been summarized by different members of our community,
many people still insist on using counterproductive radical messages,
provoking additional skepticism and closing doors that would otherwise
be open.

Conclusion

We all strive to be healthy and independent for as long as possible, to
do more things we love together with people we love. Remember, humanity
has made significant progress in defeating communicable diseases in less
than a century. Our knowledge is expanding and we could become
the first generation free from age-related diseases — if only we set
such a goal, and make an effort to reach it together. Bringing aging
under reasonable medical control is not an easy thing to do, but if we
divide the problem up into actionable pieces, and if we are serious
about getting our piece done, we will have a chance to build a better
future for everyone. A future where every person on the planet could
enjoy healthy and productive life at any age.